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Biomarkers in Alzheimer’s disease: role in early and differential diagnosis and recognition of atypical variants

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Dubois, Bruno, von Arnim, Christine A. F., Burnie, Nerida, Bozeat, Sasha, Cummings, Jeffrey·2023·Alzheimer's Research & Therapy
DOI 10.1186/s13195-023-01314-6PMC PMC10571241
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Abstract

Background: Development of in vivo biomarkers has shifted the diagnosis of Alzheimer’s disease (AD) from the later dementia stages of disease towards the earlier stages and has introduced the potential for pre-symptomatic diagnosis. The International Working Group recommends that AD diagnosis is restricted in the clinical setting to people with specific AD phenotypes and supportive biomarker findings. Main body: In this review, we discuss the phenotypic presentation and use of biomarkers for the early diagnosis of typical and atypical AD and describe how this can support clinical decision making, benefit patient communication, and improve the patient journey. Early diagnosis is essential to optimize the benefits of available and emerging treatments. As atypical presentations of AD often mimic other dementias, differential diagnosis can be challenging and can be facilitated using AD biomarkers. However, AD biomarkers alone are not sufficient to confidently diagnose AD or predict disease progression and should be supplementary to clinical assessment to help inform the diagnosis of AD. Conclusions: Use of AD biomarkers with incorporation of atypical AD phenotypes into diagnostic criteria will allow earlier diagnosis of patients with atypical clinical presentations that otherwise would have been misdiagnosed and treated inappropriately. Early diagnosis is essential to guide informed discussion, appropriate care and support, and individualized treatment. It is hoped that disease-modifying treatments will impact the underlying AD pathology; thus, determining the patient’s AD phenotype will be a critical factor in guiding the therapeutic approach and the assessment of the effects of interventions.

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  • AD diagnosis relies on detecting amyloid and tau pathology via PET, MRI, and CSF analysis.

    “AD diagnosis relies on detecting amyloid and tau pathology via positron emission tomography (PET), magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis [8,9,10].”

    From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [10]

    The PET markers and CSF biomarkers sections describe tests for amyloid and tau pathology. The MRI markers section instead describes structural MRI as showing atrophy and neurodegeneration, not directly detecting amyloid and tau. The section on clinical assessment also says biomarkers supplement, rather than replace, clinical assessment for AD diagnosis (page numbers unavailable in our copy). (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Major advances have been made in fluid and imaging biomarkers to diagnose and track AD progression in clinical trials.

    “Major advances have been made in fluid and imaging biomarkers to diagnose and track AD progression in clinical trials [17]; however, biomarker discovery in the senescence field is in its infancy [18].”

    From Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease (2025) · cites this paper as [17]

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Cited by

Sorted by citations

Authors
Dubois, B., von Arnim, C. A. F., Burnie, N., Bozeat, S., & Cummings, J.
Affiliations
  • Sorbonne Université (FR)
  • F. Hoffmann-La Roche AG (CH)
  • University of Nevada, Las Vegas (US)
ORCID
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2023-10-13
Volume
15
Issue
1
Pages
175-175
ISSN
1758-9193 (ISSN-L)
DOI
10.1186/s13195-023-01314-6
PMC
PMC10571241
OpenAlex
W4387601800
Cited by
288
References
13
Citations by year
2026: 91 · 2025: 133 · 2024: 62 · 2023: 2
FWCI
13.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
Roche Diagnostics International Ltd, Rotkreuz, Switzerland
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
Alzheimer's disease, biomarkers, early diagnosis, differential diagnosis, atypical Alzheimer's disease, presymptomatic diagnosis, diagnostic criteria, disease-modifying therapy, patient communication
MeSH terms
Alzheimer Disease, Diagnosis, Differential, Humans, Biomarkers, Disease Progression, Recognition, Psychology

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